Insulin binding to erythrocytes was shown to lack any relationship to age-related factors of the erythrocyte such as the pyruvate kinase activity and the reticulocyte count in individuals with a normal erythropoiesis. After density separation of the erythrocytes in both normal adults and children and in individuals with increased erythropoiesis, a correlation to age-factors was evident (pyruvate kinase activity/insulin binding r = 0.59, p less than 0.01, reticulocyte count/insulin binding r = 0.44, p less than 0.01). An estimate of the components of variation in the binding showed that the unexplained variance is 60%. In the density separated samples the insulin binding correlated closer to the pyruvate kinase activity than to the number of reticulocytes. During treatment of haematopoietic diseases in the 4 patients with increased erythropoiesis, the disappearance rate for the reticulocyte count was much faster (T 1/2 = 9 days) than that of the insulin binding to erythrocytes (T 1/2 = 37 days) and that of pyruvate kinase activity (T 1/2 = 36 days). In one patient studied after splenectomy, the decrease in insulin binding paralleled the disappearance curve for 51Cr-tagged erythrocytes. These results suggest that insulin binds to erythrocytes, not only during the reticulocyte stage, but throughout their life span, though the binding, which is very closely related to their pyruvate kinase activity, steadily declines as the erythrocytes age.